PDF(Pubmed)
Abstract：
Amyloid β-peptide (Aβ) synthesis and deposition are the primary factors underlying the pathophysiology of Alzheimer\'s disease (AD). Aβ oligomer (Aβo) exerts its neurotoxic effects by inducing oxidative stress and lesions by adhering to cellular membranes. Though several antidepressants have been investigated as neuroprotective agents in AD, a detailed comparison of their neuroprotection against Aβo-induced neurotoxicity is lacking. Here, we aimed to elucidate the neuroprotective effects of clinically prescribed selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants at the cellular level and establish the underlying mechanisms for their potential clinical applications. Therefore, we compared the neuroprotective effects of three antidepressants, fluoxetine (Flx), duloxetine (Dlx), and mirtazapine (Mir), by their ability to prevent oxidative stress-induced cell damage, using SH-SY5Y cells, by evaluating cell viability, generation of reactive oxygen species (ROS) and mitochondrial ROS, and peroxidation of cell membrane phospholipids. These antidepressants exhibited potent antioxidant activity (Dlx > Mir > Flx) and improved cell viability. Furthermore, pretreatment with a 5-hydroxytryptamine 1A (5-HT1A) antagonist suppressed their effects, suggesting that the 5-HT1A receptor is involved in the antioxidant mechanism of the antidepressants\' neuroprotection. These findings suggest the beneficial effects of antidepressant treatment in AD through the prevention of Aβ-induced oxidative stress.
摘要：
淀粉样β肽(Aβ)的合成和沉积是阿尔茨海默病(AD)病理生理学的主要因素。Aβ寡聚体（Aβo）通过粘附在细胞膜上诱导氧化应激和损伤而发挥其神经毒性作用。尽管已经研究了几种抗抑郁药作为AD的神经保护剂，缺乏对Aβo诱导的神经毒性的神经保护作用的详细比较。这里,我们旨在阐明临床处方选择性5-羟色胺再摄取抑制剂的神经保护作用，5-羟色胺-去甲肾上腺素再摄取抑制剂，以及细胞水平的去甲肾上腺素能和特异性5-羟色胺能抗抑郁药，并建立了其潜在临床应用的潜在机制。因此,我们比较了三种抗抑郁药的神经保护作用，氟西汀(Flx),度洛西汀（Dlx），和米氮平（Mir），通过它们防止氧化应激诱导的细胞损伤的能力，使用SH-SY5Y细胞，通过评估细胞活力，活性氧（ROS）和线粒体ROS的产生，细胞膜磷脂的过氧化。这些抗抑郁药表现出有效的抗氧化活性(Dlx>Mir>Flx)和改善的细胞活力。此外，用5-羟色胺1A（5-HT1A）拮抗剂预处理抑制了它们的作用，提示5-HT1A受体参与抗抑郁药神经保护的抗氧化机制。这些发现表明通过预防Aβ诱导的氧化应激在AD中抗抑郁治疗的有益效果。
